In the study proposed here we will analyze the biochemistry and function of myocardial hypertrophy. We will try to induce two types of cardiac hypertrophy, namely physiologic and pathologic hypertrophy, in the isolated perfused guinea pig heart. Hypertrophy will be assessed by increased protein synthesis. We will try to determine if the early genetic activation of the two types of hypertrophy, one where there is an increased myosin ATPase activity after three weeks of pressure overload and the other where there is a decrease in the rate of ATP hydrolysis after three weeks of pressure overload in the whole animal, have different effects on the early stages of myosin and other myofibrillar protein synthesis and phosphorylation in the isolated perfused working heart. Some of the analyses made to distinguish the two types of hypertrophy are rate of synthesis of various myofibrillar proteins, namely myosin, troponin, tropomyosin and actin, as well as phosphorylation of these myofibrillar proteins. Using the perfused isolated heart, we can obtain highly labeled myosin which can be specifically hydrolyzed for peptide mapping and thus determine if the myosin synthesized under the two hypertrophying conditions is a new or modified type of myosin and whether it is different between physiologic and pathologic hypertrophy. We can further assess whether one hypertrophying stimulus relative to the other can increase the tissue PCO2 of the perfused heart and whether tissue acidity can then change the calcium binding characteristics of regulated actomyosin.